Doubt over effectiveness of cholinesterase inhibitors for treatment of Alzheimer's disease

The embargo time on this release has been changed since it was first submitted. NB. Please note that if you are outside North America, the embargo for LANCET press material is 0001 hours UK Time 25 June 2004.

Authors of a UK study in this week's issue of THE LANCET conclude that the most widely used drugs to treat Alzheimer's disease (AD) have only minimal efficacy, and that an alternative approach for treatment is needed.

Around 400,000 people in the UK have AD. A class of drugs called cholinesterase inhibitors have been found to cause small increases in tests of mental ability among AD patients, although questions remain over their long-term efficacy and cost-effectiveness.

Richard Gray from the University of Birmingham, UK, and colleagues investigated whether donepezil (a cholinesterase inhibitor licensed in the UK in 1997) produced worthwhile improvements in disability, dependency, behavioural and psychological symptoms, wellbeing of carers, or delay in institutionalisation. In the study (called AD2000), 565 AD patients were randomly allocated either donepezil (5 mg or 10 mg) or placebo.

Donepezil did improve tests of mental and functional ability over the first 2 years of treatment, although at low levels. However, there was no significant delay in institutionalisation (42% donepezil, 44% placebo at 3 years), or progression of disability (58% for patients given donepezil, 59% for patients given placebo). There were also no differences between donepezil and placebo in behavioural and psychological symptoms, formal care costs, unpaid caregiver time, adverse events or deaths, or between the two doses of donepezil used in the study.

In an accompanying Commentary (p 2100), Lon S Schneider from the University of Southern California, USA, concludes: "Results [of the study] are incompatible with many drug-company-sponsored observational studies and advertisements claiming remarkable effects for cholinesterase inhibitors. For example, claims that donepezil stabilises cognitive decline, or delays nursing-home placement by 2-5 years now can be seen as implausible in the light of AD2000".

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.